Pharmacodynamic Effects, Safety and Tolerability of Cilobradine, Compared to Metoprolol Succinate and Placebo in Healthy Volunteers

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 119

Inclusion Criteria

All participants in the study should be healthy males and females. Volunteers will
- be 21 to 55 years of age
- have a Body Mass Index (BMI) of 19.9 to 29.9 kg/m2 and
- have a resting heart rate (HR) (after 10 min. in the supine position) of more than 55 beats per minute (bpm)
Only post-menopausal females, or those who had had a hysterectomy, could participate. All females had to have a negative pregnancy test
In accordance with good clinical practice (GCP) and the local legislation all volunteers had to give their written informed consent prior to admission to the study

Exclusion Criteria

Any finding of the medical examination (including BP, HR and ECG) deviating from normal and of clinical relevance
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Diseases of the central nervous system or psychiatric disorders or neurological disorders
History of relevant orthostatic hypotension, fainting spells or blackouts
Chronic or relevant acute infections
History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the Investigator
Intake of drugs with a long half-life (> 24 hours) within ten half-lives of the respective drug before enrolment in the study
Use of any drugs which might influence the results of the trial within two weeks prior to administration or during the trial
Participation in another trial with an investigational drug (≤ two months prior to administration or during the trial)
Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day)
Inability to refrain from smoking on trial days
Alcohol abuse (> 60 g/day)
Drug abuse
Blood donation (≥ 100 ml within four weeks prior to administration or during the trial)
Excessive physical activities (within the last week before the study)
Any laboratory value outside the reference range of clinical relevance

Not necessarily clinically relevant abnormalities, but specific Exclusion criteria for the drugs under study or for the study:

Consumption of more than 2 cups of coffee or black tea, or cola drinks, per day during the last 6 weeks. However, subjects may participate if abstinence from the before mentioned beverages is well tolerated during an interval of at least 2 weeks between screening and first treatment
ECG: PQ interval > 210 ms
HR at rest < 55 bpm
Systolic BP < 115 mmHg
Colour vision test abnormal. However, subjects may participate if they are able to perform the flicker fusion test without difficulty
Psoriasis (own medical history or relative)
Relevant ophthalmological disease
History of asthma or obstructive pulmonary disease
History (including childhood) of traumatic injury to the head or brain
History (including childhood) of reduced seizure threshold
The following subjects will not be allowed to participate in the study
- Any subject involved in professional transportation of human subjects
- Any subject involved in operating dangerous machinery

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cilobradine high dose 1	Cilobradine high dose 1	-
Placebo	Placebo	-
Cilobradine low dose 1	Cilobradine low dose 1	-
Cilobradine high dose 2	Cilobradine high dose 2	-
Cilobradine low dose 2	Cilobradine low dose 2	-
Cilobradine medium dose	Cilobradine medium dose	-
Metoprolol succinate	Metoprolol succinate tablets	1 tablet on day 1, day 2 followed by two tablets from day 3 to day 14

Primary Outcome Measures

Name	Time	Method
Changes in heart rate during exercise	Pre-dose, up to day 20 after first drug administration
Changes in heart rate at rest	Pre-dose, up to day 20 after first drug administration
Changes in flicker fusion frequency test (FFF)	Pre-dose, up to day 20 after first drug administration

Secondary Outcome Measures

Name	Time	Method
Number of patients with clinically relevant changes in vital signs (blood pressure, heart rate)	Pre-dose, up to 12 days after last drug administration
Changes in peripheral FFF	Pre-dose, up to day 20 after first drug administration
Area under the concentration-time curve of the analytes in plasma (AUC)	Up to day 20 after start of first drug administration
Terminal half-life of the analytes in plasma (t½)	Up to day 20 after start of first drug administration
Number of patients with clinically relevant changes in laboratory tests	Pre-dose, up to 12 days after last drug administration
Assessment of global tolerability by the investigator	Up to 12 days after last drug administration
Maximum measured concentration of the analytes in plasma (Cmax)	Up to day 20 after start of first drug administration
Time from dosing to the maximum concentration of the analytes in plasma (tmax)	Up to day 20 after start of first drug administration
Number of patients with clinically relevant changes in 12-lead ECG	Pre-dose, up to 12 days after last drug administration
Total clearance of the analytes in plasma following extravascular administration (CL/F)	Up to day 20 after start of first drug administration
Apparent volume of distribution of the analytes during the terminal phase λz following extravascular administration (Vz/F)	Up to day 20 after start of first drug administration
Number of patients with adverse events	Up to 12 days after last drug administration
Mean residence time of the analytes in the body after oral administration (MRTpo)	Up to day 20 after start of first drug administration

Pharmacodynamic Effects, Safety and Tolerability of Cilobradine, Compared to Metoprolol Succinate and Placebo in Healthy Volunteers

Recruitment & Eligibility

Study & Design

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